Introduction
Background
Metastases from carcinoma are by far the most common malignant tumors involving the skeleton. Imaging has an important role in the detection, diagnosis, prognostication, treatment planning, and follow-up monitoring of bone metastases. In patients with proven nonskeletal tumors, imaging is useful for screening the skeleton to assess metastatic disease and, if it is present, to determine its extent.1,2,3 In a patient without a known malignancy, a possible diagnosis of bone metastases may be made by recognizing radiographic and other imaging findings. If bone metastases are present or suspected, further imaging or imaging-guided techniques may be required to confirm the diagnosis, to establish the extent of the disease, and to find the primary tumor.
Pathophysiology
Metastases involve bone by means of 3 main mechanisms: (1) direct extension, (2) retrograde venous flow, and (3) seeding with tumor emboli via the blood circulation. Seeding occurs initially in the red marrow; this process accounts for the predominant distribution of metastatic lesions in the red marrow–containing areas in adults. In contrast, bone metastases are usually widespread in children. Retrograde venous embolism is probably the major mechanism when spread from intra-abdominal cancer involves the vertebrae. Increased intra-abdominal pressure causes blood to be diverted from the systemic caval system to the valveless vertebral venous plexus of Batson; this diversion allows the caudal and cranial flow of blood.
As a metastatic lesion grows in the medullary cavity, the surrounding bone is remodeled by means of either osteoclastic or osteoblastic processes. The relative degree of resultant bone resorption or deposition is highly variable and depends on the type and location of the tumor. The relationship between the osteoclastic and osteoblastic remodeling processes determines whether a predominant lytic, sclerotic, or mixed pattern is seen on radiographs.4,5
Related Medscape topics:
CME New Therapeutic Approaches for Patients With Stage III Colorectal Cancer
Resource Center Cancer: Biologic Therapies
Frequency
United States
The true incidence of bone metastases is the subject of much debate, and it is not fully known. The probability of bone metastasis originating from a primary site can be assessed only by knowing the prevalence of the cancer and its predilection for bone. Therefore, the frequency of bone metastases depends on the prevalence of the cancer in a particular community. The incidence of bone metastases also depends on the source of the data. For example, results from autopsy studies and from bone scintigraphic studies are different for newly diagnosed, established, and end-stage cancers.
For overall frequencies of carcinoma-caused bone metastases in North America, see Sex.
International
The frequency of carcinoma-caused bone metastases depends on the prevalence of a particular cancer in a given community. The probability of bone metastasis can be assessed only by knowing the regional and local prevalence of the cancer and its predilection for bone.
Mortality/Morbidity
- Bone metastases significantly limit the patient's quality of life and life expectancy.
- Patients with bone metastases frequently have reduced mobility, pain, and bone weakness that predisposes them to pathologic fractures, spinal epidural compression, and bone marrow failure.
Race
- The frequency of carcinoma-caused metastases depends on the prevalence of a particular cancer in a given race.
- The probability of bone metastasis can be assessed only by knowing the prevalence of the cancer and its predilection for bone in a particular racial group.
Sex
The frequency of carcinoma-caused bone metastases depends on its prevalence in male or female patients.- In North America, overall frequencies of carcinoma-caused bone metastases for both sexes involve the following areas, in descending order of frequency: breast, prostate, lung, colon, stomach, bladder, uterus, rectum, thyroid, and kidney.
- In North America, carcinoma-caused bone metastases in men involve the following areas, in descending order of frequency: prostate, lung, bladder, stomach, rectum, and colon.
- ln North America, carcinoma-caused bone metastases in women involve the following areas, in descending order of frequency: breast, uterus, colon, stomach, rectum, and bladder.
Metastatic Cancer, Unknown Primary Site
Related Medscape topics:
CME: Highlights of the American Society for Therapeutic Radiology and Oncology 49th Annual Meeting
CME Excess Body Weight Increases Risk for Many Cancers
CME What's New in HER2-Targeted Therapy for Breast Cancer?
Age
Bone metastases are usually found in middle-aged and elderly persons. Bone metastases are much less common in children than in adults.
- Seeding occurs initially in the red marrow; this process accounts for the predominant distribution of metastatic lesions in the red marrow–containing areas in adults.
- Bone metastases are usually widespread in children. In children, the most common causes of widespread metastases are neuroblastoma and leukemia; other tumors are relatively rare.
Related Medscape topics:
CME Treatment Advances in Leukemia
CME FDA Approvals: Campath and Norditropin
Anatomy
Bone metastases are often multiple at the time of diagnosis. In adults, the lesions generally occur in the axial skeleton and other sites with residual red marrow, although the lesions may be found anywhere in the skeletal system. Common sites for metastases are the vertebrae, pelvis, proximal parts of the femur, ribs, proximal part of the humerus, and skull. More than 90% of metastases are found in this distribution.
Certain carcinomas may have a predilection for particular skeletal sites. For example, metastases to the bones of the hands and feet are rare, but 50% of hand metastases originate from lung neoplasms (see Image 1). Primary tumors arising from the pelvis have a predilection for spread to the lumbosacral spine.
Presentation
In patients with a known primary carcinoma, the development of bone pain usually is considered to be highly suggestive of bone metastases. However, Schaberg and Gainor found that 36% of patients with spinal metastases did not complain of bone pain.6 Galasko and Sylvester also found that only 66% of their patients with back pain and a history of previous malignancy had bone metastases.7 Occasionally, patients with bone metastases may present with a pathologic fracture; therefore, checking the state of underlying bone for disease is important if such a fracture is suspected (see Image 2).8 In addition, patients may present with complications of bone metastases, such as neurologic impairment due to spinal epidural compression (see Image 3).
Preferred Examination
Technetium-99m (99m Tc) bone scintiscanning (ie, radionuclide bone scanning) is widely regarded as the most cost-effective and available whole-body screening test for the assessment of bone metastases. Conventional radiography is the best modality for characterizing lesions that are depicted on bone scintiscans. Combined analysis and reporting of findings on radiographs and99m Tc bone scintiscans improve the diagnostic accuracy in detecting bone metastases and assessing the response to therapy.9,10,11
CT and MRI are useful in evaluating suspicious bone scintiscan findings that appear equivocal on radiographs.12,13,14,15 MRI can also help in detecting metastatic lesions before changes in bone metabolism make the lesions detectable on bone scintiscans.16,17,18 CT is useful in guiding needle biopsy, particularly in vertebral lesions. MRI is helpful in determining the extent of local disease in planning surgery or radiation therapy.
The first screening test used for the detection of bone metastases depends on the relative availability of MRI and99m Tc bone scintiscanning. The selection will become less of an issue when more MRI units are established and when its cost decreases. Factors such as cost and relatively long imaging times, as well as considerations of patient throughput, are important. MRI is estimated to cost 2-3 times as much as99m Tc bone scintigraphy19,20 ; fluorodeoxyglucose (FDG) positron emission tomography (PET) costs 8 times as much.21,22,23,24,25
Limitations of Techniques
Radiographs are relatively insensitive in the detection of early or small metastatic lesions. Although CT scans are superior to radiographs, CT is also relatively insensitive in showing small intramedullary lesions, and it has the disadvantage of limited skeletal coverage. Bone scintiscan findings are sensitive but nonspecific. Whole-body MRI and FDG-PET are accurate techniques that are currently limited by their high cost.26,27,28,29,30
Differential Diagnoses
Other Problems to Be Considered
Secondary osteoarthritis
More on Bone Metastases |
 Overview: Bone Metastases |
| Imaging: Bone Metastases |
| Follow-up: Bone Metastases |
| Multimedia: Bone Metastases |
| References |
| Next Page » |
References
Downey SE, Wilson M, Boggis C, et al. Magnetic resonance imaging of bone metastases: a diagnostic and screening technique. Br J Surg. Aug 1997;84(8):1093-4. [Medline].
Peh WC. Screening for bone metastases. Am J Orthop. May 2000;29(5):405. [Medline].
Traill ZC, Talbot D, Golding S, Gleeson FV. Magnetic resonance imaging versus radionuclide scintigraphy in screening for bone metastases. Clin Radiol. Jul 1999;54(7):448-51. [Medline].
Salmon JM, Kilpatrick SE. Pathology of skeletal metastases. Orthop Clin North Am. Oct 2000;31(4):537-44, vii-viii. [Medline].
Clines GA, Guise TA. Molecular mechanisms and treatment of bone metastasis. Expert Rev Mol Med. Mar 6 2008;10:e7. [Medline].
Schaberg J, Gainor BJ. A profile of metastatic carcinoma of the spine. Spine. Jan-Feb 1985;10(1):19-20. [Medline].
Galasko CS, Sylvester BS. Back pain in patients treated for malignant tumours. Clin Oncol. Sep 1978;4(3):273-83. [Medline].
Baker LL, Goodman SB, Perkash I, et al. Benign versus pathologic compression fractures of vertebral bodies: assessment with conventional spin-echo, chemical-shift, and STIR MR imaging. Radiology. Feb 1990;174(2):495-502. [Medline].
Bellamy EA, Nicholas D, Ward M, et al. Comparison of computed tomography and conventional radiology in the assessment of treatment response of lytic bony metastases in patients with carcinoma of the breast. Clin Radiol. Jul 1987;38(4):351-5. [Medline].
Libshitz HI, Hortobagyi GN. Radiographic evaluation of therapeutic response in bony metastases of breast cancer. Skeletal Radiol. 1981;7(3):159-65. [Medline].
Merrick MV, Beales JS, Garvie N, Leonard RC. Evaluation and skeletal metastases. Br J Radiol. Sep 1992;65(777):803-6. [Medline].
Aitchison FA, Poon FW, Hadley MD, et al. Vertebral metastases and an equivocal bone scan: value of magnetic resonance imaging. Nucl Med Commun. Jun 1992;13(6):429-31. [Medline].
Evans AJ, Robertson JF. Magnetic resonance imaging versus radionuclide scintigraphy for screening in bone metastases. Clin Radiol. Aug 2000;55(8):653; discussion 653-4. [Medline].
Gosfield E 3rd, Alavi A, Kneeland B. Comparison of radionuclide bone scans and magnetic resonance imaging in detecting spinal metastases. J Nucl Med. Dec 1993;34(12):2191-8. [Medline].
Steiner RM, Mitchell DG, Rao VM, Schweitzer ME. Magnetic resonance imaging of diffuse bone marrow disease. Radiol Clin North Am. Mar 1993;31(2):383-409. [Medline].
Algra PR, Bloem JL, Tissing H, et al. Detection of vertebral metastases: comparison between MR imaging and bone scintigraphy. Radiographics. Mar 1991;11(2):219-32. [Medline].
Frank JA, Ling A, Patronas NJ, et al. Detection of malignant bone tumors: MR imaging vs scintigraphy. AJR Am J Roentgenol. Nov 1990;155(5):1043-8. [Medline].
Kattapuram SV, Khurana JS, Scott JA, el-Khoury GY. Negative scintigraphy with positive magnetic resonance imaging in bone metastases. Skeletal Radiol. 1990;19(2):113-6. [Medline].
Dickinson F, Liddicoat A, Dhingsa R, Finlay D. Magnetic resonance imaging versus radionuclide scintigraphy for screening in bone metastases. Clin Radiol. Aug 2000;55(8):653. [Medline].
Merrick MV. Bone scintigraphy--an update. Clin Radiol. May 1989;40(3):231-2. [Medline].
Ell PJ. Skeletal imaging in metastatic disease. Curr Opin Radiol. Dec 1991;3(6):791-6. [Medline].
Gold RI, Seeger LL, Bassett LW, Steckel RJ. An integrated approach to the evaluation of metastatic bone disease. Radiol Clin North Am. Mar 1990;28(2):471-83. [Medline].
Jaovisidha S, Subhadrabandhu T, Siriwongpairat P, Pochanugool L. An integrated approach to the evaluation of osseous tumors. Orthop Clin North Am. Jan 1998;29(1):19-39. [Medline].
Kagan AR, Bassett LW, Steckel RJ, Gold RH. Radiologic contributions to cancer management. Bone metastases. AJR Am J Roentgenol. Aug 1986;147(2):305-12. [Medline].
Martin WH, Delbeke D, Patton JA, Sandler MP. Detection of malignancies with SPECT versus PET, with 2-[fluorine- 18]fluoro-2-deoxy-D-glucose. Radiology. Jan 1996;198(1):225-31. [Medline].
Aoki J, Inoue T, Tomiyoshi K, et al. Nuclear imaging of bone tumors: FDG-PET. Semin Musculoskelet Radiol. Jun 2001;5(2):183-7. [Medline].
Cook GJ, Fogelman I. Detection of bone metastases in cancer patients by 18F-fluoride and 18F- fluorodeoxyglucose positron emission tomography. Q J Nucl Med. Mar 2001;45(1):47-52. [Medline].
Cook GJ, Fogelman I. The role of positron emission tomography in the management of bone metastases. Cancer. Jun 15 2000;88(12 Suppl):2927-33. [Medline].
Delbeke D, Martin WH. Positron emission tomography imaging in oncology. Radiol Clin North Am. Sep 2001;39(5):883-917. [Medline].
Schirrmeister H, Guhlmann A, Kotzerke J, et al. Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography. J Clin Oncol. Aug 1999;17(8):2381-9. [Medline].
Hortobagyi GN, Libshitz HI, Seabold JE. Osseous metastases of breast cancer. Clinical, biochemical, radiographic, and scintigraphic evaluation of response to therapy. Cancer. Feb 1 1984;53(3):577-82. [Medline].
Rutgers EJ, van Slooten EA, Kluck HM. Follow-up after treatment of primary breast cancer. Br J Surg. Feb 1989;76(2):187-90. [Medline].
Sanal SM, Flickinger FW, Caudell MJ, Sherry RM. Detection of bone marrow involvement in breast cancer with magnetic resonance imaging. J Clin Oncol. Jul 1994;12(7):1415-21. [Medline].
Petrut B, Trinkaus M, Simmons C, Clemons M. A primer of bone metastases management in breast cancer patients. Curr Oncol. Jan 2008;15(Supplement 1):S50-7. [Medline].
Pollen JJ, Reznek RH, Talner LB. Lysis of osteoblastic lesions in prostatic cancer: a sign of progression. AJR Am J Roentgenol. Jun 1984;142(6):1175-9. [Medline].
Kuhlman JE, Fishman EK, Leichner PK, et al. Skeletal metastases from hepatoma: frequency, distribution, and radiographic features. Radiology. Jul 1986;160(1):175-8. [Medline].
Muindi J, Coombes RC, Golding S, et al. The role of computed tomography in the detection of bone metastases in breast cancer patients. Br J Radiol. Apr 1983;56(664):233-6. [Medline].
Durning P, Best JJ, Sellwood RA. Recognition of metastatic bone disease in cancer of the breast by computed tomography. Clin Oncol. Dec 1983;9(4):343-6. [Medline].
Steinborn MM, Heuck AF, Tiling R, et al. Whole-body bone marrow MRI in patients with metastatic disease to the skeletal system. J Comput Assist Tomogr. Jan-Feb 1999;23(1):123-9. [Medline].
Eustace S, Tello R, DeCarvalho V, et al. A comparison of whole-body turbo STIR MR imaging and planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases. AJR Am J Roentgenol. Dec 1997;169(6):1655-61. [Medline].
Jones AL, Williams MP, Powles TJ, et al. Magnetic resonance imaging in the detection of skeletal metastases in patients with breast cancer. Br J Cancer. Aug 1990;62(2):296-8. [Medline].
Schweitzer ME, Levine C, Mitchell DG, et al. Bull's-eyes and halos: useful MR discriminators of osseous metastases. Radiology. Jul 1993;188(1):249-52. [Medline].
Flickinger FW, Sanal SM. Bone marrow MRI: techniques and accuracy for detecting breast cancer metastases. Magn Reson Imaging. 1994;12(6):829-35. [Medline].
Shih TT, Huang KM, Li YW. Solitary vertebral collapse: distinction between benign and malignant causes using MR patterns. J Magn Reson Imaging. May 1999;9(5):635-42. [Medline].
Baur A, Stabler A, Bruning R, et al. Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology. May 1998;207(2):349-56. [Medline].
Le Bihan DJ. Differentiation of benign versus pathologic compression fractures with diffusion-weighted MR imaging: a closer step toward the "holy grail" of tissue characterization?. Radiology. May 1998;207(2):305-7. [Medline].
Peh WC, Gilula LA, Zeller D. Percutaneous vertebroplasty: a new technique for treatment of painful compression fractures. Mo Med. Mar 2001;98(3):97-102. [Medline].
Moulopoulos LA, Yoshimitsu K, Johnston DA, et al. MR prediction of benign and malignant vertebral compression fractures. J Magn Reson Imaging. Jul-Aug 1996;6(4):667-74. [Medline].
Rupp RE, Ebraheim NA, Coombs RJ. Magnetic resonance imaging differentiation of compression spine fractures or vertebral lesions caused by osteoporosis or tumor. Spine. Dec 1 1995;20(23):2499-503; discussion 2504. [Medline].
Spuentrup E, Buecker A, Adam G, et al. Diffusion-weighted MR imaging for differentiation of benign fracture edema and tumor infiltration of the vertebral body. AJR Am J Roentgenol. Feb 2001;176(2):351-8. [Medline].
Castillo M, Arbelaez A, Smith JK, Fisher LL. Diffusion-weighted MR imaging offers no advantage over routine noncontrast MR imaging in the detection of vertebral metastases. AJNR Am J Neuroradiol. May 2000;21(5):948-53. [Medline].
Chan JH, Peh WC, Tsui EY, Chau LF, Cheung KK, Chan KB, et al. Acute vertebral body compression fractures: discrimination between benign and malignant causes using apparent diffusion coefficients. Br J Radiol. Mar 2002;75(891):207-14. [Medline].
Krishnamurthy GT, Tubis M, Hiss J, Blahd WH. Distribution pattern of metastatic bone disease. A need for total body skeletal image. JAMA. Jun 6 1977;237(23):2504-6. [Medline].
McKeage K, Plosker GL. Zoledronic Acid: a pharmacoeconomic review of its use in the management of bone metastases. Pharmacoeconomics. 2008;26(3):251-68. [Medline].
Zelinka T, Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Reynolds JC, et al. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations. Endocr Relat Cancer. Mar 2008;15:(1):311-323. [Medline].
Daldrup-Link HE, Franzius C, Link TM, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR Am J Roentgenol. Jul 2001;177(1):229-36. [Medline].
Ohta M, Tokuda Y, Suzuki Y, et al. Whole body PET for the evaluation of bony metastases in patients with breast cancer: comparison with 99Tcm-MDP bone scintigraphy. Nucl Med Commun. Aug 2001;22(8):875-9. [Medline].
Kao CH, Hsieh JF, Tsai SC, et al. Comparison and discrepancy of 18F-2-deoxyglucose positron emission tomography and Tc-99m MDP bone scan to detect bone metastases. Anticancer Res. May-Jun 2000;20(3B):2189-92. [Medline].
Franzius C, Sciuk J, Daldrup-Link HE, et al. FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy. Eur J Nucl Med. Sep 2000;27(9):1305-11. [Medline].
Jonsson K, Johnell O. Preoperative angiography in patients with bone metastases. Acta Radiol Diagn (Stockh). 1982;23(5):485-9. [Medline].
Maxon HR 3rd, Schroder LE, Thomas SR, et al. Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. Jul 1990;176(1):155-9. [Medline].
McEwan AJ. Palliative therapy with bone seeking radiopharmaceuticals. Cancer Biother Radiopharm. Dec 1998;13(6):413-26. [Medline].
Krishnamurthy GT, Krishnamurthy S. Radionuclides for metastatic bone pain palliation: a need for rational re-evaluation in the new millennium. J Nucl Med. Apr 2000;41(4):688-91. [Medline].
Taylor AJ Jr. Strontium-89 for the palliation of bone pain due to metastatic disease. J Nucl Med. Dec 1994;35(12):2054. [Medline].
Cotten A, Dewatre F, Cortet B, et al. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of the percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology. Aug 1996;200(2):525-30. [Medline].
Deramond H, Depriester C, Galibert P, Le Gars D. Percutaneous vertebroplasty with polymethylmethacrylate. Technique, indications, and results. Radiol Clin North Am. May 1998;36(3):533-46. [Medline].
Weill A, Chiras J, Simon JM, et al. Spinal metastases: indications for and results of percutaneous injection of acrylic surgical cement. Radiology. Apr 1996;199(1):241-7. [Medline].
Cortet B, Cotten A, Boutry N, et al. Percutaneous vertebroplasty in patients with osteolytic metastases or multiple myeloma. Rev Rhum Engl Ed. Mar 1997;64(3):177-83. [Medline].
Barton PP, Waneck RE, Karnel FJ, et al. Embolization of bone metastases. J Vasc Interv Radiol. Jan-Feb 1996;7(1):81-8. [Medline].
Siberstein EB. Advances in our understanding of the treatment of painful bone metastasis. J Nucl Med. Apr 2000;41(4):655-7. [Medline].
Kopelman D, Inbar Y, Hanannel A, Pfeffer RM, Dogadkin O, Freundlich D, et al. Magnetic resonance guided focused ultrasound surgery. Ablation of soft tissue at bone-muscle interface in a porcine model. Eur J Clin Invest. Apr 2008;38(4):268-75. [Medline].
Further Reading
Keywords
bone secondaries, skeletal metastases, bone metastasis, metastases, metastasis, bone lesions
